2. Academic Validation
  3. Cell cycle control of wnt receptor activation

Cell cycle control of wnt receptor activation

  • Dev Cell. 2009 Dec;17(6):788-99. doi: 10.1016/j.devcel.2009.11.006.
Gary Davidson 1,  Jinlong Shen,  Ya-Lin Huang,  Yi Su,  Emil Karaulanov,  Kerstin Bartscherer,  Christine Hassler,  Peter Stannek,  Michael Boutros,  Christof Niehrs
Affiliations

Affiliation

  • 1 Division of Molecular Embryology, Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann von Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany. [email protected]
PMID: 20059949 DOI: 10.1016/j.devcel.2009.11.006
Abstract

Low-density lipoprotein receptor related proteins 5 and 6 (LRP5/6) are transmembrane receptors that initiate Wnt/beta-catenin signaling. Phosphorylation of PPPSP motifs in the LRP6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide RNAi screen, we show that PPPSP phosphorylation requires the Drosophila Cyclin-dependent kinase (CDK) L63. L63 and its vertebrate homolog PFTK are regulated by the membrane tethered G2/M Cyclin, Cyclin Y, which mediates binding to and phosphorylation of LRP6. As a consequence, LRP6 phosphorylation and Wnt/beta-catenin signaling are under cell cycle control and peak at G2/M phase; knockdown of the mitotic regulator CDC25/string, which results in G2/M arrest, enhances Wnt signaling in a Cyclin Y-dependent manner. In Xenopus embryos, Cyclin Y is required in vivo for LRP6 phosphorylation, maternal Wnt signaling, and Wnt-dependent anteroposterior embryonic patterning. G2/M priming of LRP6 by a Cyclin/CDK complex introduces an unexpected new layer of regulation of Wnt signaling.

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